Effect of medium-chain triglycerides supplements and walking on health-related quality of life in sedentary, healthy middle-aged, and older adults with low BMIs: a randomized, double-blind, placebo-controlled, parallel-group trial.

Introduction: To extend individuals' healthy life expectancies, the improvement of subjective health and quality of life (QOL) has been increasingly prioritized, alongside the improvement of their physical functioning. Reports have indicated that intake of medium-chain triglycerides (MCTs) benefits the physical health of older individuals requiring nursing care, and athletes, and healthy individuals. But there are few studies investigating the effects of MCTs on subjective health and QOL. The present study sought to evaluate the combined effects of 12-week MCTs supplements and moderate-intensity walking exercise on the subjective health and QOL of middle-aged and older adults aged 60-74 with low BMIs (< 24 kg/m2) and who had no exercise habits. Methods: A placebo-controlled, double-blind, parallel-group trial was conducted. Three MCTs supplement groups with different doses and fatty acid compositions were compared with a control group. The study used the SF-36v2 questionnaire to assess subjective health and health-related QOL (HRQOL). Results: The result showed significant improvements in the scores on subscales of the physical QOL, such as Physical functioning and General health, and summary scores on the mental QOL, compared to the control. Conclusion: It is estimated that the combination of continuous intake of MCTs and walking exercise may affect HRQOL and improve subjective physical and mental health in sedentary, healthy, middle-aged and older adults. Clinical trial registration: https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046861, UMIN000046861.

Effect of Low Protein Diets Supplemented with Sodium Butyrate, Medium-Chain Fatty Acids, or n-3 Polyunsaturated Fatty Acids on the Growth Performance, Immune Function, and Microbiome of Weaned Piglets.

This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 healthy weaned piglets ((Landrace × Large White × Duroc); 7.93 ± 0.7 kg initial body weight), were randomly divided into five groups. Each group consisted of six replications with four piglets per replication. Dietary treatments included control diet (CON); LP diet (LP); LP + 0.2% SB diet (LP + SB); LP + 0.2% MCT diet (LP + MCT); and LP + PUFA diet (LP + PUFA). The experimental period lasted for 4 weeks. Compared with the CON diet, LP, LP + SB, LP + MCT, and LP + PUFA diets decreased the final weight and average daily gain (ADG) of piglets (p < 0.05). There were lower (p < 0.05) concentrations of IL-8 and higher (p < 0.05) Glutathione peroxidase (GSH-Px) activity in the plasma of piglets fed with LP + SB, LP + MCT, and LP + PUFA diets than those fed with the LP diet. The piglets in the LP + SB and LP + PUFA groups had lower IKK-alpha (IKKa) mRNA expression in the colonic mucosa compared with those in the CON and LP groups (p < 0.05). The mRNA expression of TLR4 in the colonic mucosa of piglets in the LP + SB, LP + MCT, and LP + PUFA groups was decreased when compared with the CON and LP groups (p < 0.05). The LP + MCT diets increased the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosa of piglets compared with CON, LP, and LP + SB diets (p < 0.05). The abundance of Erysipelotrichaceae in the colonic microbiome of piglets in the LP group was higher than that in the other four groups (p < 0.05). Collectively, this study showed that LP diets supplemented with SB, MCT, or n-3 PUFA reduced plasma inflammatory factor levels, increased plasma GSH-Px activity, and declined mRNA expression of TLR4 and IKKa in the colonic epithelium, whereas it reduced the abundance of Erysipelotrichaceae in the colon of piglets.

Resveratrol-Loaded Attalea funifera Oil Organogel Nanoparticles: A Potential Nanocarrier against A375 Human Melanoma Cells.

This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

A Randomized, Double-Blind, Controlled Trial Assessing If Medium-Chain Triglycerides in Combination with Moderate-Intensity Exercise Increase Muscle Strength in Healthy Middle-Aged and Older Adults.

An adequate nutritional intake is recommended for the prevention of physical frailty and sarcopenia. In particular, medium-chain fatty acids (MCFAs) are reportedly important for muscle strength in nursing home residents. However, the effects of MCFAs on healthy adults at risk for frailty remain unknown. Hence, a randomized, placebo-controlled study was conducted to investigate the effects of 12 weeks of medium-chain triglycerides (MCTs) intake and walking on muscle mass and function in healthy, sedentary, middle-aged and older adults with a low body mass index. Three MCT intake groups with different amounts of octanoic and decanoic acid intake were compared with a control group. After 12 weeks, knee extension strength increased in all groups, with the increases in all MCT intake groups being significantly higher than those in the control group (p < 0.05). Grip strength significantly increased from baseline in the MCT 6 g/day intake group (p < 0.05). The combination of aerobic exercise and MCT intake may be effective in preventing decline in muscle strength and promoting increase in muscle strength as they can improve muscle energy production, thereby contributing to the maintenance of good health for middle-aged and older adults at high risk for frailty and sarcopenia.

Feeding medium-chain fatty acid-rich formula causes liver steatosis and alters hepatic metabolism in neonatal pigs.

Medium-chain fatty acids (MCFA) and long-chain fatty acids (LCFAs) are often added to enhance the caloric value of infant formulas. Evidence suggests that MCFAs promote growth and are preferred over LCFAs due to greater digestibility and ease of absorption. Our hypothesis was that MCFA supplementation would enhance neonatal pig growth to a greater extent than LCFAs. Neonatal pigs (n = 4) were fed a low-energy control (CONT) or two isocaloric high-energy formulas containing fat either from LCFAs, or MCFAs for 20 days. Pigs fed the LCFAs had greater body weight compared with CONT- and MCFA-fed pigs (P < 0.05). In addition, pigs fed the LCFAs and MCFAs had more body fat than those in the CONT group. Liver and kidney weights as a percentage of body weight were greater (P ≤ 0.05) for pigs fed the MCFAs than those fed the CONT formula, and in those fed LCFAs, liver and kidney weights as a percentage of body weight were intermediate (P ≤ 0.05). Pigs in the CONT and LCFA groups had less liver fat (12%) compared with those in the MCFA (26%) group (P ≤ 0.05). Isolated hepatocytes from these pigs were incubated in media containing [13C]tracers of alanine, glucose, glutamate, and propionate. Our data suggest alanine contribution to pyruvate is less in hepatocytes from LCFA and MCFA pigs than those in the CONT group (P < 0.05). These data suggest that a formula rich in MCFAs caused steatosis compared with an isocaloric LCFA formula. In addition, MCFA feeding can alter hepatocyte metabolism and increase total body fat without increasing lean deposition.NEW & NOTEWORTHY Our data suggest that feeding high-energy MCFA formula resulted in hepatic steatosis compared with isoenergetic LCFA or low-energy formulas. Steatosis coincided with greater laurate, myristate, and palmitate accumulation, suggesting elongation of dietary laurate. Data also suggest that hepatocytes metabolized alanine and glucose to pyruvate, but neither entered the tricarboxylic acid (TCA) cycle. In addition, the contribution of alanine and glucose was greater for the low-energy formulas compared with the high-energy formulas.

Fecal Microbiota, Bile Acids, Sterols, and Fatty Acids in Dogs with Chronic Enteropathy Fed a Home-Cooked Diet Supplemented with Coconut Oil.

Medium-chain fatty acids (MCFAs) are considered to be interesting energy sources for dogs affected by chronic enteropathies (CE). This study analyzed the clinical scores, fecal microbiota, and metabolomes of 18 CE dogs fed a home-cooked diet (HCD) supplemented with virgin coconut oil (VCO), a source of MCFA, at 10% of metabolizable energy (HCD + VCO). The dogs were clinically evaluated with the Canine Chronic Enteropathy Activity Index (CCECAI) before and at the end of study. Fecal samples were collected at baseline, after 7 days of HCD, and after 30 days of HCD + VCO, for fecal score (FS) assessment, microbial analysis, and determination of bile acids (BA), sterols, and fatty acids (FA). The dogs responded positively to diet change, as shown by the CCECAI improvement (p = 0.001); HCD reduced fecal fat excretion and HCD + VCO improved FS (p < 0.001), even though an increase in fecal moisture occurred due to HCD (p = 0.001). HCD modified fecal FA (C6:0: +79%, C14:0: +74%, C20:0: +43%, C22:0: +58%, C24:0: +47%, C18:3n-3: +106%, C20:4n-6: +56%, and monounsaturated FA (MUFA): -23%, p < 0.05) and sterol profile (coprostanol: -27%, sitostanol: -86%, p < 0.01). VCO increased (p < 0.05) fecal total saturated FA (SFA: +28%, C14:0: +142%, C16:0 +21%, C22:0 +33%) and selected MCFAs (+162%; C10:0 +183%, C12:0 +600%), while reducing (p < 0.05) total MUFA (-29%), polyunsaturated FA (-26%), campesterol (-56%) and phyto-/zoosterols ratio (0.93:1 vs. 0.36:1). The median dysbiosis index was <0 and, together with fecal BA, was not significantly affected by HCD nor by VCO. The HCD diet increased total fecal bacteria (p = 0.005) and the abundance of Fusobacterium spp. (p = 0.028). This study confirmed that clinical signs, and to a lesser extent fecal microbiota and metabolome, are positively influenced by HCD in CE dogs. Moreover, it has been shown that fecal proportions of MCFA increased when MCFAs were supplemented in those dogs. The present results emphasize the need for future studies to better understand the intestinal absorptive mechanism of MCFA in dogs.

Medium chain fatty acid supplementation improves animal metabolic and immune status during the transition period: A study on dairy cattle.

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows' health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.

Supplementation with medium-chain fatty acids increases body weight loss during very low-calorie ketogenic diet: a retrospective analysis in a real-life setting.

BACKGROUND: Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD. METHODS: In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation - 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation - 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention. RESULTS: MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02-3.36) also after adjusting for the potential confounding factors. CONCLUSION: MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention.

Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis.

CONTEXT: In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. OBJECTIVE: This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. DATA SOURCES: A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. DATA EXTRACTION: Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. DATA ANALYSIS: All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. CONCLUSION: MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019146967.

Performance and gut health status of broilers fed diets supplemented with two graded levels of a monoglyceride blend.

The present study was undertaken to evaluate the efficacy of 2 graded levels (0.03 and 0.05% of diet) of a monoglyceride blend containing butyric, caprylic, and capric acids in broilers' diet for optimizing gut structure and animal growth performance. For this purpose, a total of 210, one-day-old male Ross 308 broiler chicks were randomly allocated to 3 experimental treatments using 7 replicates each and 10 birds/replicate. The treatment groups involved supplementation of blend of short and medium chain fatty acids at the level of 0, 0.03, and 0.05% of the diet for 42 d. The incorporation of mixes of monoglycerides into broilers' diet linearly improved BWG between d 0 and 21 (P = 0.034). At the end of trial, however, no significant changes were observed in performance indexes (BWG, FI, FCR). Jejunal morphometric parameters (villus height, crypt depth, and their ratio) remained unaltered with the monoglyceride supplementation on d 21. The results further showed that monoglycerides supplementation increased the goblet cell counts along the jejunal villi (P = 0.034) and crypt regions (P = 0.022), as well as it effectively modulated the mRNA abundances of tight junction protein (ZO-1, P = 0.033) and nutrient transporters (SGLT, PePT1; P = 0.005, 0.023, respectively) in the jejunum. Moreover, the downregulation in mRNA abundance of TNFα (P = 0.030) was observed with the monoglyceride supplementation. The SCFAs analysis of cecal contents showed no notable differences with monoglyceride blend supplementation when compared to the unsupplemented group. Collectively, high goblet cell numbers in the jejunum along with downregulation of the mRNA abundances of pro-inflammatory cytokines, upregulation of tight junction proteins, and nutrient transporters showed favorable responses of low doses of monoglycerides blend in broiler feeding. Further studies should be conducted in different rearing conditions to examine the effectiveness of such low levels of a monoglyceride blend in the modulation of gut structure, its functionality and animal performance.

Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome.

BACKGROUND & AIMS: Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that magnesium (Mg) supplementation leads to enhanced gut microbial production of MCFAs and, in turn, increased circulating MCFAs levels. METHODS: We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants. Six 24-h dietary recalls were performed for all participants at the baseline and during the intervention period. Based on the baseline 24-h dietary recalls, the Mg treatment used a personalized dose of Mg supplementation that would reduce the calcium (Ca): Mg intake ratio to around 2.3. We measured plasma MCFAs, sugars, ketone bodies and tricarboxylic acid cycle (TCA cycle) metabolites using the Metabolon's global Precision Metabolomics™ LC-MS platform. Whole-genome shotgun metagenomics (WGS) sequencing was performed to assess microbiota in stool samples, rectal swabs, and rectal biopsies. RESULTS: Personalized Mg treatment (mean dose 205.58 mg/day with a range from 77.25 to 389.55 mg/day) significantly increased the plasma levels of C7:0, C8:0, and combined C7:0 and C8:0 by 18.45%, 25.28%, and 24.20%, respectively, compared to 14.15%, 10.12%, and 12.62% decreases in the placebo arm. The effects remain significant after adjusting for age, sex, race and baseline level (P = 0.0126, P = 0.0162, and P = 0.0031, respectively) and FDR correction at 0.05 (q = 0.0324 for both C7:0 and C8:0). Mg treatment significantly reduced the plasma level of sucrose compared to the placebo arm (P = 0.0036 for multivariable-adjusted and P = 0.0216 for additional FDR correction model) whereas alterations in daily intakes of sucrose, fructose, glucose, maltose and C8:0 from baseline to the end of trial did not differ between two arms. Mediation analysis showed that combined C7:0 and C8:0 partially mediated the effects of Mg treatment on total and individual ketone bodies (P for indirect effect = 0.0045, 0.0043, and 0.03, respectively). The changes in plasma levels of C7:0 and C8:0 were significantly and positively correlated with the alterations in stool microbiome α diversity (r = 0.51, p = 0.0023 and r = 0.34, p = 0.0497, respectively) as well as in stool abundance for the signatures of MCFAs-related microbiota with acyl-ACP thioesterase gene producing C7:0 (r = 0.46, p = 0.0067) and C8:0 (r = 0.49, p = 0.003), respectively, following Mg treatment. CONCLUSIONS: Optimizing Ca:Mg intake ratios to around 2.3 through 12-week personalized Mg supplementation leads to increased circulating levels of MCFAs (i.e. C7:0 and C8:0), which is attributed to enhanced production from gut microbial fermentation and, maybe, sucrose consumption.

Effect of medium-chain fatty acids on growth, health, and immune response of dairy calves.

It is necessary for the dairy industry to reduce calf morbidity and mortality, and the reliance on antibiotics to treat sick calves, to address the growing concern regarding antibiotic resistant bacteria. The primary objective of this study was to evaluate the effect that feeding dairy calves medium-chain fatty acids (MCFA) has on growth performance and health, and the secondary objective was to evaluate the effect of MCFA on energy status around weaning and the adaptive immune response following a vaccine challenge. Thirty-three Holstein bull calves (5 ± 1.6 d of age) were randomly assigned to 1 of 2 treatments. Control (CON) calves were fed milk replacer with no C8:0 or C10:0 oil added and MCFA calves were fed milk replacer with 0.5% of a combination of C8:0 or C10:0 oil added. Body weight and average daily gain were measured weekly. Feed efficiency (gain/feed) and the change in body condition score, hip width, hip height, heart girth, and paunch girth were calculated for the duration of the study. Fecal scores were recorded daily and all medical treatments were documented for the duration of the trial. On d 42, 49, and 56 of the study, a serum sample was collected from each calf and used to measure nonesterified fatty acids, ß-hydroxybutyric acid, insulin, and glucose concentrations to evaluate energy status around weaning. A subset of 11 calves per treatment were enrolled in a vaccine challenge. At 21 ± 1.9 d of age (mean ± standard deviation) calves were vaccinated intramuscularly with 1 mL of endotoxin-free ovalbumin (OVA) mixed with aluminum hydroxide adjuvant. At 42 d of age (±1.9 d), blood samples were collected and used to analyze OVA-specific IgG1 and IgG2, and calves were vaccinated a second time. At 56 d of age (±1.9 d), blood samples were collected to analyze IgG1 and IgG2 as well as IFN-γ and IL-4 secreted from peripheral blood mononuclear cells (PBMC) treated with OVA or phytohemagglutinin. Data were analyzed as a completely randomized design with repeated measures when applicable. A tendency for greater daily fecal score was observed for MCFA calves compared with CON. At d 42 of the study, nonesterified fatty acid concentrations were greater in CON calves compared with MCFA. At 42 and 56 d of age, anti-OVA IgG1 concentrations for CON and MCFA calves were greater than prevaccination samples. This study suggests that feeding MCFA to calves affects the energy status of calves around weaning and vaccinating dairy calves with ovalbumin combined with an aluminum hydroxide adjuvant is an effective way to evaluate the adaptive immune responses.

Supplementation of Regular Diet With Medium-Chain Triglycerides for Procognitive Effects: A Narrative Review.

It is now widely accepted that ketosis (a physiological state characterized by elevated plasma ketone body levels) possesses a wide range of neuroprotective effects. There is a growing interest in the use of ketogenic supplements, including medium-chain triglycerides (MCT), to achieve intermittent ketosis without adhering to a strict ketogenic diet. MCT supplementation is an inexpensive and simple ketogenic intervention, proven to benefit both individuals with normal cognition and those suffering from mild cognitive impairment, Alzheimer's disease, and other cognitive disorders. The commonly accepted paradigm underlying MCT supplementation trials is that the benefits stem from ketogenesis and that MCT supplementation is safe. However, medium-chain fatty acids (MCFAs) may also exert effects in the brain directly. Moreover, MCFAs, long-chain fatty acids, and glucose participate in mutually intertwined metabolic pathways. Therefore, the metabolic effects must be considered if the desired procognitive effects require administering MCT in doses larger than 1 g/kg. This review summarizes currently available research on the procognitive effects of using MCTs as a supplement to regular feed/diet without concomitant reduction of carbohydrate intake and focuses on the revealed mechanisms linked to particular MCT metabolites (ketone bodies, MCFAs), highlighting open questions and potential considerations.

Conversion of Short and Medium Chain Fatty Acids into Novel Polyhydroxyalkanoates Copolymers by Aeromonas sp. AC_01.

Polyhydroxyalkanoates (PHAs) production by Aeromonas sp. AC_01 was investigated using synthetic and waste derived short and medium chain fatty acids (SMCFAs). The obtained results revealed that the analyzed bacterial strain was able to grow and synthesize PHAs using SMCFAs. The highest PHA productivity was observed in the cultivation supplemented with a mixture of acetic acid and butyric acid (3.89 mg/L·h). Furthermore, SMCFAs-rich stream, derived from acidogenic mixed culture fermentation of acid whey, was found to be less beneficial for PHA productivity than its synthetic mixture, however the PHA production was favored by the nitrogen-limited condition. Importantly, Aeromonas sp. AC_01 was capable of synthesizing novel scl-mcl copolymers of 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 3-hydroxytridecanoate (3HtriD) and/or 3-hydroxytetradecaonate (3HTD) with high 3HB and 3HV fractions. They were identified with alterable monomers composition depending on the culture conditions used. Moreover, in-depth thermal analyses proved that they are highly resistant to thermal degradation regardless of their monomeric composition. The obtained results confirm that Aeromonas sp. AC_01 is a promising candidate for the biotechnological production of PHAs from SMCFAs with thermal properties that can be tuned together with their chemical composition by the corresponding adjustment of the cultivation process.

Short and Medium Chain Fatty Acids and Their Derivatives as a Natural Strategy in the Control of Necrotic Enteritis and Microbial Homeostasis in Broiler Chickens.

The use of antibiotic growth promoters (AGPs) has historically been the most important prophylactic strategy for the control of Necrotic Enteritis (NE) caused by some Clostridium perfringens toxin types in poultry. During the last five decades, AGPs have also been supplemented in feed to improve body weight gain and feed efficiency as well as to modulate the microbiome (consisting of microbes and their genes both beneficial and potentially harmful) and reduce enteric pathogens, among other benefits. New regulatory requirements and consumer preferences have led to strong interest in natural alternatives to the AGPs for the prevention and control of illnesses caused by enteric pathogens. This interest is not just focused on the direct removal or inhibition of the causative microorganisms but also the improvement of intestinal health and homeostasis using a range of feed additives. A group of promising feed additives is short- and medium-chain fatty acids (SCFA and MCFA, respectively) and their derivatives. The use of SCFA and MCFA, including butyric, caproic, caprylic, capric, and lauric acids, has shown strong effects against NE in broilers both at experimental and commercial levels. These fatty acids also benefit intestinal health integrity and homeostasis. Other effects have also been documented, including increases in intestinal angiogenesis and gene expression of tight junctions. Chemical modifications to improve stability and point of release in the intestine have been shown to improve the efficacy of SCFA and MCFA and their derivatives. The aim of this review is to give an overview of SCFA, MCFA and their derivatives, as an alternative to replace AGPs to control the incidence and severity of NE in poultry.

Medium-Chain Triglyceride Oil and Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Dietary saturated fat raises total cholesterol and LDL cholesterol levels. It is unclear whether these effects differ by the fatty acid chain lengths of saturated fats; particularly, it is unclear whether medium-chain fatty acids increase lipid levels. OBJECTIVES: We conducted a systematic review to determine the effects of medium-chain triglyceride (MCT) oil, consisting almost exclusively of medium-chain fatty acids (6:0-10:0), on blood lipids. METHODS: We searched Medline and Embase through March 2020 for randomized trials with a minimum 2-week intervention period that compared MCT oil with another fat or oil. Outcomes were total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. Included studies were restricted to adults above 18 years of age. Studies conducted in populations receiving enteral or parenteral nutrition were excluded. Data were pooled using a random-effects meta-analysis. RESULTS: Seven articles were included in the meta-analysis; LDL cholesterol and HDL cholesterol were reported in 6 studies. MCT oil intake did not affect total cholesterol (0.04 mmol/L; 95% CI, -0.11 to 0.20; I2 = 33.6%), LDL cholesterol (0.02 mmol/L; 95% CI, -0.13 to 0.17; I2 = 28.7%), or HDL cholesterol (-0.01 mmol/L; 95% CI, -0.10 to 0.09; I2 = 74.1%) levels, but did increase triglycerides (0.14 mmol/L; 95% CI, 0.01-0.27; I2 = 42.8%). Subgroup analyses showed that the effects of MCT oil on total cholesterol and LDL cholesterol differed based on the fatty acid profile of the control oil (Pinteraction = 0.003 and 0.008, respectively), with MCT oil increasing total cholesterol and LDL cholesterol when compared to a comparator consisting predominantly of unsaturated fatty acids, and with some evidence for reductions when compared to longer-chain SFAs. CONCLUSIONS: MCT oil does not affect total cholesterol, LDL cholesterol, or HDL cholesterol levels, but does cause a small increase in triglycerides.

Exploring the metabolic fate of medium-chain triglycerides in healthy individuals using a stable isotope tracer.

BACKGROUND & AIMS: Medium chain triglyceride (MCT) supplementation is often recommended as treatment for patients with long-chain fatty acid ß-oxidation (lcFAO) disorders, since they can be utilized as an energy source without the use of the defective enzyme. However, studies in mice and preterm infants suggest that not all medium-chain fatty acids (MCFA) are oxidized and may undergo elongation to long-chain fatty acids (LCFA). In this single blinded study, we explored the metabolic fates of MCT in healthy individuals using a 13C-labeled MCT tracer. METHOD: Three healthy males in rest received on two test days a primed continuous infusion of glyceryl tri[1,2,3,4-13C4]-octanoate with either an isocaloric supplementation of 1) exclusively MCT (MCT-only) or 2) a mixture of MCT, proteins and carbohydrates (MCT-mix). Gas chromatography - combustion - isotope ratio mass spectrometry (GC-C-IRMS) was used to determine 13C-enrichment of long-chain fatty acids in plasma and of 13CO2 in exhaled air. RESULTS: When provided as single energy source, an estimated 42% of administered MCT was converted to CO2. In combination with carbohydrates and proteins in the diet, oxidation of MCT was higher (62%). In both diets <1% of 13C-label was incorporated in LCFA in plasma, indicating that administered MCT underwent chain-elongation to LCT. CONCLUSIONS: Although the relative MCT oxidation rate was higher when combined with carbohydrates and protein, quantitatively more MCT was oxidized when given an isocaloric meal with solely MCT. As these results were obtained in the resting state opposed to during exercise, it is too early to give a recommendation concerning the use of MCT in lcFAO disorders. The data show that in resting healthy individuals only a very small part of the MCT is traced back as LCFA in plasma, suggesting that MCT treatment does not result in a large LCFA burden, however further research on storage of MCT in tissues is warranted. REGISTRATION: The study was registered in the Nederlands Trialregister. Protocol ID: Trial NL7417 (NTR7650).

Bioconversion of swine manure into high-value products of medium chain fatty acids.

This research proposes and demonstrates, for the first time, the utilization of swine manure as a complex feedstock to produce high-value medium chain fatty acids (MCFA). The two-stage anaerobic digestion (AD) carboxylates platform was adopted for the conversion of swine manure to short chain fatty acids (SCFAs) and then SCFAs to MCFA (n-caproate, n-heptanoate, and n-caprylate) with ethanol supplementation. We defined the appropriate initial pH of 10.0 for SCFAs production with a carbon conversion rate of 71.2%, and acetate, propionate were the main products, which accounted for around 72.9% of the total SCFAs in the primary stage (I). Through the addition of ethanol, 61.3% of the converted carbon in the complex SCFAs solution was converted into MCFA (C6-C8) in the chain elongation stage (II), while only 6.7% was attributed to methane formation. The concentrations of n-caproate, n-heptanoate, and n-caprylate reached 8.6 g COD/L (3.9 g/L), 6.4 g COD/L (2.7 g/L), and 2.6 g COD/L (1.07 g/L), respectively. This study achieved a relatively higher concentration of n-heptanoate compared with past studies of MCFA from other feedstock. These findings demonstrated a new route for resource recovery and the operating parameters for producing MCFA from swine manure.

Effect of Maternal Diet and Medium Chain Fatty Acids Supplementation for Piglets on Their Digestive Tract Development, Structure, and Chyme Acidity as Well as Performance and Health Status.

The objective of the present study was to evaluate the effect of oils for sows during late pregnancy and lactation on offspring performance. In addition, the effect of caprylic acid (C8) or medium-chain triglyceride oil (MCT) in piglets' feed on their gut development, performance, and health status was determined. The experiment was conducted on 24 sows allocated to two treatments: diet with rapeseed oil or with coconut oil. Newborn piglets were randomly allocated to three treatments: feed with no supplement or supplemented with 0.3% MCT or with 0.3% C8. The results showed that both oils had no effect on sow reproductive rates; however, fatty acid patterns of milk differed significantly and the number of lost piglets was lower in sow fed with coconut oil. Both caprylic and MCT oil significantly improved piglet performance and villus height. These additives did not change triacylglycerol content in blood, but C8 lowered total cholesterol and MCT increased IgG content. It can be concluded that coconut oil fed to pregnant and lactating sows can markedly reduce the mortality of piglets and that caprylic acid and medium-chain fatty acid oil can be a good supplement in weaned piglet feed.

Curcumin Nanoemulsions Stabilized with Modified Phosphatidylcholine on Skin Carcinogenesis Protocol.

BACKGROUND: Cancer is one of the main causes of death by disease; several alternative treatments have been developed to counteract this condition. Curcumin (diferuloylmethane), extracted from the rhizome of Curcuma longa, has antioxidant, anti-inflammatory, and anti-cancer properties; however, it has low water solubility and poor intestinal absorption. Carrier systems, such as nanoemulsions, can increase the bioavailability of lipophilic bioactive compounds. OBJECTIVE: To evaluate the effect of curcumin nanoemulsions prepared with lecithin modified with medium-chain fatty acids as an emulsifier, on the expression of the Cdk4, Ccne2, Casp8 and Cldn4 genes involved in the carcinogenesis process in K14E6 transgenic mice. METHODS: The emulsifier was prepared by interesterification of medium-chain fatty acids, pure lecithin, and immobilized phospholipase-1 on Duolite A568. An Ultraturrax homogenizer and a Branson Ultrasonic processor were used for the preparation of nano-emulsions, and a Zetasizer evaluated the particle size. qRT-PCR analysis was performed to quantify the cancer-related genes expressed in the K14E6 mice. The development and evolution of skin carcinogenesis were assessed through histological analysis to compare cell morphology. RESULTS: Ca 59% of the MCFA were incorporated via esterification into the PC within 12 hours of the reaction. An emulsifier yield used to formulate the NE of 86% was achieved. Nanoemulsions with a particle size of 44 nm were obtained. The curcumin nano-emulsion group had a 91.81% decrease in the tumorigenesis index and a reduction in tumor area of 89.95% compared to the sick group. Histological analysis showed that the group administered with free curcumin developed a microinvasive squamous cell carcinoma, as opposed to the group with nanoemulsion which presented only a slight inflammation. In gene expression, only a significant difference in Cdk4 was observed in the nanoemulsion group.